Objective: To determine the clinical performance of partial coverage restorations (PCR) (onlays, occlusal veneers, and partial crowns) composed of different ceramic and ceramic-based materials to treat extended posterior defects. Materials and Methods: MEDLINE, Scopus, CENTRAL, ClinicalTrials.gov, and the International Clinical Trials Registry Platform were searched (inception-February 2024) for randomized controlled trials (RCT) comparing posterior PCRs composed of different ceramic and ceramic-based materials with a minimum follow-up of 1 year. Results: Six RCTs were included. Resin matrix ceramic (RMC) and lithium disilicate (LDS) restorations had a 3-year survival rate of 89.3% (95% CI 76.4–95.3) and 93.7% (95% CI 83.7–97.7), respectively, and leucite-reinforced glass ceramic (LRGC) restorations a range between 96.1% (95% CI 90.1–98.9) compared with RMC and 98.3% (95% CI 90.8–100) compared with LDS. After 1–3 years of follow-up, LDS slightly outperformed RMC on restoration failure and loss of retention (1.56 more failures and 1.78 more loss of retentions for RMC per 100 restoration-years [low certainty evidence]). No statistically significant differences between ceramic and ceramic-based materials were detected in short-term follow-up (1–3 years of follow-up). The long-term performance of posterior PCRs is uncertain. Conclusion: The survival of LDS restorations may slightly outperform RMC restorations after 3 years of follow-up across outcomes, except for bulk fracture. RCTs providing medium to long-term data are needed. Clinical Significance: Ceramic and ceramic-based PCRs are a reliable treatment option to restore extended posterior defects.